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Aims/hypothesis <p>In healthy men, lauric acid (C12) and <span>l</span>-tryptophan (Trp), when administered intraduodenally in loads of 1.26 and 0.42 kJ/min (0.3 and 0.1 kcal/min), respectively, that are individually ineffective, stimulate glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK), when combined. Both hormones slow gastric emptying, suppress energy intake and lower postprandial glucose. We have now investigated the hypothesis that combined intraduodenal administration of these nutrients reduces postprandial glucose in type 2 diabetes.</p> Methods <p>In a randomised, blinded (investigators and participants), crossover study performed in the University of Adelaide Clinical Research Facility, 11 men with type 2 diabetes (age: 69&#xa0;±&#xa0;7 years; HbA<sub>1</sub>c: 51&#xa0;±&#xa0;5 mmol/mol [6.8&#xa0;±&#xa0;0.3%]; BMI: 28&#xa0;±&#xa0;1 kg/m<sup>2</sup>), each received, on four separate occasions, 45 min intraduodenal infusions of C12 (1.26 kJ/min), Trp (0.42 kJ/min), C12+Trp (1.68 kJ/min), or 0.9% saline (control), 30 min before a mixed-nutrient drink (350 ml, 2092 kJ (500&#xa0;kcal), 74 g carbohydrate) containing 100 mg <sup>13</sup>C-acetate. Plasma glucose, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), insulin, C-peptide and CCK concentrations were measured at baseline, following treatments alone, and for 180 min post-drink. Gastric emptying was assessed via <sup>13</sup>C-acetate breath test.</p> Results <p>C12+Trp, but not C12 or Trp, reduced overall (<i>p</i>=0.02) and peak (mmol/l; control: 11.1&#xa0;±&#xa0;0.6, Trp: 10.3&#xa0;±&#xa0;0.5, C12: 10.7&#xa0;±&#xa0;0.6, C12+Trp: 9.8&#xa0;±&#xa0;0.5; <i>p</i>=0.01) plasma glucose. C12+Trp slowed gastric emptying (<i>p</i>=0.001), and increased pre-drink plasma GLP-1, GIP and CCK (all <i>p</i>&lt;0.05), without affecting insulin or C-peptide. No treatment effects were observed postprandially.</p> Conclusions/interpretation <p>In type 2 diabetes, intraduodenal C12+Trp lowers postprandial glucose, probably primarily by slowing of gastric emptying and mediated by GLP-1 and CCK. These findings support further exploration of nutrient-based gastrointestinal strategies to optimise glycaemic management in type 2 diabetes.</p> Trial registration <p>Australian New Zealand Clinical Trials Registry (<a href="http://www.anzctr.org.au">www.anzctr.org.au</a>) ACTRN12623000778684</p> Funding <p>JAS and VB were each supported by Adelaide Scholarship International stipends, provided by the University of Adelaide (JAS, 2021–2025; VB, 2017–2020) and CFB by a National Health and Medical Research Council (NHMRC) Senior Research Fellowship (Grant 1103020, 2016–2023). The research was supported by a Diabetes Australia Research Project Grant (2021–2022) to CFB.</p> Graphical Abstract <p></p>

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Effects of combined intraduodenal administration of lauric acid and l-tryptophan on postprandial plasma glucose, glucoregulatory hormones and gastric emptying in type 2 diabetes: a double-blind, randomised, crossover study

  • 期刊论文

  • 发表日期：

    2025年12月19日

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  • Javad Anjom-Shoae,
  • Penelope C. E. Fitzgerald,
  • Braden D. Rose,
  • Vida Bitarafan,
  • Jens F. Rehfeld,
  • Michael Horowitz,
  • Christine Feinle-Bisset

摘要

Aims/hypothesis

In healthy men, lauric acid (C12) and l-tryptophan (Trp), when administered intraduodenally in loads of 1.26 and 0.42 kJ/min (0.3 and 0.1 kcal/min), respectively, that are individually ineffective, stimulate glucagon-like peptide-1 (GLP-1) and cholecystokinin (CCK), when combined. Both hormones slow gastric emptying, suppress energy intake and lower postprandial glucose. We have now investigated the hypothesis that combined intraduodenal administration of these nutrients reduces postprandial glucose in type 2 diabetes.

Methods

In a randomised, blinded (investigators and participants), crossover study performed in the University of Adelaide Clinical Research Facility, 11 men with type 2 diabetes (age: 69 ± 7 years; HbA1c: 51 ± 5 mmol/mol [6.8 ± 0.3%]; BMI: 28 ± 1 kg/m2), each received, on four separate occasions, 45 min intraduodenal infusions of C12 (1.26 kJ/min), Trp (0.42 kJ/min), C12+Trp (1.68 kJ/min), or 0.9% saline (control), 30 min before a mixed-nutrient drink (350 ml, 2092 kJ (500 kcal), 74 g carbohydrate) containing 100 mg 13C-acetate. Plasma glucose, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), insulin, C-peptide and CCK concentrations were measured at baseline, following treatments alone, and for 180 min post-drink. Gastric emptying was assessed via 13C-acetate breath test.

Results

C12+Trp, but not C12 or Trp, reduced overall (p=0.02) and peak (mmol/l; control: 11.1 ± 0.6, Trp: 10.3 ± 0.5, C12: 10.7 ± 0.6, C12+Trp: 9.8 ± 0.5; p=0.01) plasma glucose. C12+Trp slowed gastric emptying (p=0.001), and increased pre-drink plasma GLP-1, GIP and CCK (all p<0.05), without affecting insulin or C-peptide. No treatment effects were observed postprandially.

Conclusions/interpretation

In type 2 diabetes, intraduodenal C12+Trp lowers postprandial glucose, probably primarily by slowing of gastric emptying and mediated by GLP-1 and CCK. These findings support further exploration of nutrient-based gastrointestinal strategies to optimise glycaemic management in type 2 diabetes.

Trial registration

Australian New Zealand Clinical Trials Registry (www.anzctr.org.au) ACTRN12623000778684

Funding

JAS and VB were each supported by Adelaide Scholarship International stipends, provided by the University of Adelaide (JAS, 2021–2025; VB, 2017–2020) and CFB by a National Health and Medical Research Council (NHMRC) Senior Research Fellowship (Grant 1103020, 2016–2023). The research was supported by a Diabetes Australia Research Project Grant (2021–2022) to CFB.

Graphical Abstract